Atherosclerosis, a form of arteriosclerosis, is characterized by deposition of lipids in the aorta and in the coronary, cerebral and peripheral arteries of the lower extremities. As these masses increase in size, the risk of thrombosis and the ensuing occlusion arises.
Although the etiology of this disease is not fully understood, it has been found that those afflicted with atherosclerosis exhibit elevated levels of plasma lipoprotein, of which cholesterol and triglycerides are the major constituents. In addition to the recommendation that dietary habits leading to lower .beta.-lipoprotein levels be observed, various therapeutic agents such as estrogens, thyroxine analogs, sitosterol preparations and, more recently, Atromid-S (ethyl p-chlorophenoxyisobutyrate) have been used to lower cholesterol levels in individuals prone to the condition.
It has now been found that benzoic acids, and more particularly a series of polysubstituted benzoic acids are effective in reducing plasma lipid levels and can be expected to be useful in the treatment of atherosclerosis and related cardiovascular diseases associated with elevated lipid levels.
Benzoic acid derivatives have been known in the chemical literature for some time and have been reported to possess varied utilities, the most common of which is as intermediates leading to more complicated and diverse chemical structures. For example, S-phenacylthiosalicylic acids are reported, Netherlands Specification 6,607,608, to be useful in the synthesis of benzothiophenes reported to be valuable because of their analgetic, antipyretic, antiinflammatory, antitussive, local anesthetic, antispasmodic, and antihistaminic activity.
Benzoic acid derivatives are utilized in the synthesis of tricyclic dibenz[b,e]oxepines (Collect. Czech. Chem. Commun., 32, 3448, 1967; C.A., 68, 29677r, 1968) and dibenzo[b,f]thiepins (Collect. Czech. Chem. Commun., 33, 1852, 1968; C.A., 69, 86950u, 1968), useful as neurotropic and psychotropic agents.
Quinuclidinyl esters, claimed in U.S. Pat. No. 3,405,134 as central nervous stimulants, utilizes m-benzyloxybenzoic acid in the preparation of final products.
Baker, et al., J. Med. Chem., 10, 1129 (1967), has recently shown that certain phenacyloxy and acetonyloxy derivatives of benzoic acid are inhibitors of .alpha.-chymotrypsin.
Recently, m-fluorobenzoic acid has been reported, Belgium Patent 724,121, to possess analgesic, antipyretic and hypolipemic activity.